hCG-dependent regulation of angiogenic factors in human granulosa lutein cells

• Published in: Molecular reproduction and development Vol. 73; no. 7; pp. 878 - 884
• Main Authors: Phan, B., Rakenius, A., Pietrowski, D., Bettendorf, H., Keck, C., Herr, D.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.07.2006; Wiley-Liss
• Subjects: angiogenesis; Angiogenesis Inducing Agents - chemistry; Biological and medical sciences; Cells, Cultured; Chorionic Gonadotropin - metabolism; Connective Tissue Growth Factor; corpus luteum; Cytokines - genetics; Down-Regulation; Female; Fibroblast Growth Factors - genetics; Fundamental and applied biological sciences. Psychology; Granulosa Cells - metabolism; granulosa lutein cell; hCG; Hormone metabolism and regulation; Humans; Immediate-Early Proteins - genetics; Insulin-Like Growth Factor Binding Proteins - genetics; Intercellular Signaling Peptides and Proteins - genetics; Leptin - genetics; Luteal Cells - metabolism; Mammalian female genital system; Neovascularization, Physiologic; regulation; Tissue Inhibitor of Metalloproteinase-1 - genetics; Up-Regulation; Vertebrates: reproduction; Human; Angiogenic factor; angiogenesis; Gonadotropin; Gene expression; In vitro; hCG; Placental hormone; granulosa lutein cell; Ovary; Human chorionic gonadotrophin; regulation; Female genital system; corpus luteum; Granulosa; Ovarian follicle; Quantitative analysis
• ISSN: 1040-452X; 1098-2795
• DOI: 10.1002/mrd.20465

As prerequisite for development and maintenance of many diseases angiogenesis is of particular interest in medicine. Pathologic angiogenesis takes place in chronic arthritis, collagen diseases, arteriosclerosis, retinopathy associated with diabetes, and particularly in cancers. However, angiogenesis as a physiological process regularly occurs in the ovary. After ovulation the corpus luteum is formed by rapid vascularization of initially avascular granulosa lutein cell tissue. This process is regulated by gonadotropic hormones. In order to gain further insights in the regulatory mechanisms of angiogenesis in the ovary, we investigated these mechanisms in cell culture of human granulosa lutein cells. In particular, we determined the expression and production of several angiogenic factors including tissue inhibitor of matrix metalloproteinases‐1 (TIMP‐1), Leptin, connective tissue growth factor (CTGF), meningioma‐associated complimentary DNA (Mac25), basic fibroblast growth factor (bFGF), and Midkine. In addition, we showed that human chorionic gonadotropin (hCG) has distinct effects on their expression and production. hCG enhances the expression and production of TIMP‐1, whereas it downregulates the expression of CTGF and Mac25. Furthermore it decreases the expression of Leptin. Our results provide evidence that hCG determines growth and development of the corpus luteum by mediating angiogenic pathways in human granulosa lutein cells. Hence we describe a further approach to understand the regulation of angiogenesis in the ovary. Mol. Reprod. Dev. © 2006 Wiley‐Liss, Inc.